Function of type I and type II keratin head domains: their role in dimer, tetramer and filament formation

1994 ◽  
Vol 107 (7) ◽  
pp. 1959-1972 ◽  
Author(s):  
M. Hatzfeld ◽  
M. Burba
Keyword(s):  
Complete Removal ◽  
Type I ◽  
Type Ii ◽  
Head Region ◽  
Direct Role ◽  
Filament Assembly ◽  
Head Domain ◽  
Hybrid Molecules

To examine the role of the keratin head region and its subdomains in filament assembly we constructed several deletion mutants of type I and type II keratins and analysed their in vitro IF forming capacity. The delta K8 (1–74) and delta K18 (1–56), mutants formed only soluble oligomers, predominantly tetramers with their heterotypic partners. K8 mutants that retained either the entire (delta K8 (1–64)) or nearly the entire (delta K8 (1–66)) H1 subdomain formed some short and irregular IF-like structures with K18. However, filaments never reached the normal length and more protofilamentous material was observed. Analysis of the soluble complexes in 2 M guanidine-HCl indicated that tetramer formation was impaired in the truncated molecules. The length of the deletion correlated with the degree of tetramer destabilization. These results suggest that the head domain--specifically the H1 subdomain of type II keratins-plays a direct role in IF assembly. Its functions include a stabilization of the tetramer molecule, suggesting a role in directing the alignment of dimers as well as in elongation. We also analysed whether both head domains are required or if either type I or type II head domains alone are sufficient for IF formation. Hybrid molecules carrying their partner keratins head domains (K18 (8 head) and K8 (18 head)) were combined with their wild-type partners and tested for IF-forming ability. Both combinations formed filaments distinct from normal IF. The effect of the ‘replaced’ head domains was not compensated when both hybrid molecules were combined. Taken together, the results indicate that complete removal of the head domains of either K8 or K18 arrested IF assembly at the state of soluble oligomers. Replacement of the head domains by head domains of the complementary partner partly compensated for the effect. However, regular IF formation could not take place when either the head domain was missing or it was replaced by the partner's keratin head.

scholarly journals Cryo-EM Structures of Amyloid-β 42 Filaments from Human Brain

2021 ◽  
Author(s):  
Yang ` Yang ◽  
Diana Arseni ◽  
Wenjuan Zhang ◽  
Melissa Huang ◽  
Sofia Lövestam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Amyloid Β ◽  
Imaging Agents ◽  
Type I ◽  
Type Ii ◽  
Sporadic Alzheimer’S Disease ◽  
Filament Assembly

Filament assembly of amyloid-β peptides ending at residue 42 (Aβ42) is a central event in Alzheimer's disease. We report the cryo-EM structures of Aβ42 filaments from brain. Two structurally related S-shaped protofilament folds give rise to two types of filaments. Type I filaments were found mostly in the brains of individuals with sporadic Alzheimer's disease and Type II filaments in individuals with familial Alzheimer's disease and other conditions. The structures of Aβ42 filaments from brain differ from those of filaments assembled in vitro. By contrast, in App NL-F knock-in mice, Aβ42 deposits were made of Type II filaments. Knowledge of Aβ42 filament structures from human brain may lead to the development of inhibitors of assembly and improved imaging agents.

scholarly journals The roles of K5 and K14 head, tail, and R/K L L E G E domains in keratin filament assembly in vitro.

1992 ◽  
Vol 119 (2) ◽  
pp. 401-414 ◽  
Author(s):  
A K Wilson ◽  
P A Coulombe ◽  
E Fuchs
Keyword(s):  
Type I ◽  
Type Ii ◽  
Transfected Cells ◽  
Keratin 5 ◽  
Filament Assembly ◽  
Filament Structure ◽  
In Vitro Assembly ◽  
Keratin Filament ◽  
The Stability

Type I and type II keratins form obligatory heterodimers, which self-assemble into 10-nm intermediate filaments (IFs). Like all IF proteins, they have a central alpha-helical rod domain, flanked by nonhelical head and tail domains. The IF rod is more highly conserved than head and tail, and within the rod, the carboxy R/K L L E G E sequence is more highly conserved than most other regions. Mutagenesis studies have shed some light on the roles of the head, tail, and R/K L L E G E sequence in 10-nm filament structure. However, interpretations have often been complicated in part because many of these studies have focused on transfected cells, where filament structure cannot be evaluated. Of the few in vitro assembly studies thus far conducted, comparison of keratin mutants with other IF mutants have often been difficult, due to the obligatory heteropolymeric nature of keratin IFs. In this report, we describe in vitro filament assembly studies on headless, tailless, headless/tailless, and R/K L L E G E truncated mutants of keratin 5 and its partner keratin 14. Using varying conditions of ionic strength and pH, we examine effects of analogous K5 and K14 mutations on the stability of 10-nm filament structure. Using EM, we examine effects of mutations on the ability of subunits/protofibrils to (a) elongate and (b) laterally associate. Our results demonstrate that (a) tails of K5 and K14 are required for filament stabilization; (b) the head of K5, but not of K14, is required for filament elongation and lateral alignments; and (c) the R/K L L E G E domains are required for lateral alignments, but not for filament elongation.

Metabolic Changes in Human CD36 Deficiency Displayed by Glucose Loading

2001 ◽  
Vol 86 (10) ◽  
pp. 995-999 ◽  
Author(s):  
Hidekatsu Yanai ◽  
Hironobu Fujiwara ◽  
Mie Morimoto ◽  
Yukihiro Takahashi ◽  
Shu-Ping Hui ◽  
...  
Keyword(s):  
Metabolic Changes ◽  
Type I ◽  
Type Ii ◽  
Loading Test ◽  
Glucose Loading ◽  
Cd36 Deficiency ◽  
Metabolic Role

SummaryPrevious in vitro studies have shown that CD36 participates in cellular fatty acid (FA) uptake. In vivo evidence for a physiologic role of CD36 in this process is poor and mostly obtained in animals. To examine the metabolic role of human CD36, we performed a glucose loading test for normals (n = 16) and subjects with CD36 deficiency, both Type I (n = 5) and Type II (n = 16). After 30 min, FA levels had fallen by 60.1% in normals but by only 31.7% in Type II deficiency (P <0.01 vs. normals) and 16.5% in Type I deficiency which remained significantly higher than the other two groups out to 2 h. Further, changes in triglyceride and glucose metabolism were observed in the both types of CD36 deficiency. Impaired fast FA clearance by muscle and consequently increased hepatic FA uptake seem to underlie these changes. We conclude that human CD36 deficiency causes systemic metabolic changes.

scholarly journals The Role of NKT Cells in Glioblastoma

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1641
Author(s):  
Emily E. S. Brettschneider ◽  
Masaki Terabe
Keyword(s):  
Immune Responses ◽  
Cell Activity ◽  
Nkt Cells ◽  
Type I ◽  
Type Ii ◽  
Central Nervous System Diseases ◽  
Nkt Cell ◽  
Lipid Antigens ◽  
Immunoregulatory Mechanisms

Glioblastoma is an aggressive and deadly cancer, but to date, immunotherapies have failed to make significant strides in improving prognoses for glioblastoma patients. One of the current challenges to developing immunological interventions for glioblastoma is our incomplete understanding of the numerous immunoregulatory mechanisms at play in the glioblastoma tumor microenvironment. We propose that Natural Killer T (NKT) cells, which are unconventional T lymphocytes that recognize lipid antigens presented by CD1d molecules, may play a key immunoregulatory role in glioblastoma. For example, evidence suggests that the activation of type I NKT cells can facilitate anti-glioblastoma immune responses. On the other hand, type II NKT cells are known to play an immunosuppressive role in other cancers, as well as to cross-regulate type I NKT cell activity, although their specific role in glioblastoma remains largely unclear. This review provides a summary of our current understanding of NKT cells in the immunoregulation of glioblastoma as well as highlights the involvement of NKT cells in other cancers and central nervous system diseases.

scholarly journals Inhibition of hepatic deiodination of thyroxine is caused by selenium deficiency in rats

1987 ◽  
Vol 248 (2) ◽  
pp. 443-447 ◽  
Author(s):  
G J Beckett ◽  
S E Beddows ◽  
P C Morrice ◽  
F Nicol ◽  
J R Arthur
Keyword(s):  
Thyroid Hormones ◽  
Production Rate ◽  
Selenium Deficiency ◽  
Enzyme Complex ◽  
Measurable Effect ◽  
Direct Role ◽  
Mechanism Of Inhibition ◽  
Se Deficiency

Selenium (Se) deficiency produced up to a 14-fold decrease in hepatic tri-iodothyronine (T3) production from thyroxine (T4) in vitro. The T3 production rate could not be restored by the addition of a variety of cofactors, nor by the addition of control homogenate. The impairment in hepatic T3 production observed in Se deficiency was reflected in the concentrations of thyroid hormones circulating in plasma, T4 being increased approx. 40% and T3 being decreased by 30%. However, the fall in plasma T3 concentrations was smaller than might be expected in view of the marked decreased in T3 production. Se deficiency had no measurable effect on plasma reverse-tri-iodothyronine concentrations. The data suggest that Se deficiency produces an inhibition of both 5- and 5′-deiodination, consistent with the widely held view that these reactions are catalysed by the same enzyme complex. The mechanism of inhibition appears not be mediated by changes in thiol levels, but a direct role of Se in the activity of the deiodinase complex cannot be excluded.

Modeling Endoleaks and Collateral Reperfusion following Endovascular AAA Exclusion

2003 ◽  
Vol 10 (3) ◽  
pp. 424-432 ◽  
Author(s):  
Chuh K. Chong ◽  
Thien V. How ◽  
Geoffrey L. Gilling-Smith ◽  
Peter L. Harris
Keyword(s):  
Stent Graft ◽  
Aortic Pressure ◽  
Type I ◽  
Type Ii ◽  
Pump System ◽  
Type Ii Endoleak ◽  
Type I Endoleak ◽  
The Impact ◽  
Mean Aortic Pressure

Purpose: To investigate the effect on intrasac pressure of stent-graft deployment within a life-size silicone rubber model of an abdominal aortic aneurysm (AAA) maintained under physiological conditions of pressure and flow. Methods: A commercial bifurcated device with the polyester fabric preclotted with gelatin was deployed in the AAA model. A pump system generated physiological flow. Mean and pulse aortic and intrasac pressures were measured simultaneously using pressure transducers. To simulate a type I endoleak, plastic tubing was placed between the aortic wall and the stent-graft at the proximal anchoring site. Type II endoleak was simulated by means of side branches with set inflow and outflow pressures and perfusion rates. Type IV endoleak was replicated by removal of gelatin from the graft fabric. Results: With no endoleak, the coated graft reduced the mean and pulse sac pressures to negligible values. When a type I endoleak was present, mean sac pressure reached a value similar to mean aortic pressure. When net flow through the sac due to a type II endoleak was present, mean sac pressure was a function of the inlet pressure, while pulse pressure in the sac was dependent on both inlet and outlet pressures. As perfusion rates increased, both mean and pulse sac pressures decreased. When there was no outflow, mean sac pressure was similar to mean aortic pressure. In the presence of both type I and type II endoleaks, mean sac pressure reached mean aortic pressure when the net perfusion rate was low. Conclusions: In vitro studies are useful in gaining an understanding of the impact of different types of endoleaks, in isolation and in combination, on intrasac pressure after aortic stent-graft deployment.

scholarly journals Native Gold in the Chudnoe Au-Pd-REE Deposit (Subpolar Urals, Russia): Composition, Minerals in Intergrowth and Genesis

Minerals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 451
Author(s):  
Galina Palyanova ◽  
Valery Murzin ◽  
Andrey Borovikov ◽  
Nikolay Karmanov ◽  
Sergei Kuznetsov
Keyword(s):  
Native Gold ◽  
Microprobe Analysis ◽  
Electron Microprobe Analysis ◽  
Gold Mineralization ◽  
Type I ◽  
Type Ii ◽  
Subpolar Urals ◽  
Type V ◽  
Impurity Elements

Composition of native gold and minerals in intergrowth with rhyolites of the Chudnoe Au-Pd-REE deposit (Subpolar Urals, Russia) was studied using optical microscopy, scanning electron microscopy, and electron microprobe analysis. Five varieties of native gold have been identified, based on the set of impurity elements and their quantities, and on intergrown minerals. Native gold in rhyolites from the Ludnaya ore zone is homogeneous and contains only Ag (fineness 720‰, type I). It is in intergrowth with fuchsite or allanite and mertieite-II. In rhyolites from the Slavnaya ore zone, native gold is heterogeneous, has a higher fineness, different sets and contents of elements: Ag, Cu, 840–860‰ (type II); Ag, Cu, Pd, 830–890‰ (III); Ag, Pd, Cu, Hg, 840–870‰ (IV). It occurs in intergrowth with fuchsite, albite, and mertieite-II (type II), or albite, quartz, and atheneite (III), or quartz, albite, K-feldspar, and mertieite-II (IV). High fineness gold (930–1000‰, type V) with low contents of Ag, Cu, and Pd or their absence occurs in the form as microveins, fringes and microinclusions in native gold II–IV. Tetra-auricupride (AuCu) is presented as isometric inclusions in gold II and platelets in the decay structures in gold III and IV. The preliminary data of a fluid inclusions study showed that gold mineralization at the Chudnoe deposit could have been formed by chloride fluids of low and medium salinity at temperatures from 105 to 230 °C and pressures from 5 to 115 MPa. The formation of native gold I is probably related to fuchsitization and allanitization of rhyolites. The formation of native gold II-V is also associated with the same processes, but it is more complicated and occurred later with a significant role of Na-, Si-, and K-metasomatism. The presence of Pd and Cu in the ores and Cr in fuchsite indicates the important role of mafic-ultramafic magmatism.

Type VI collagen expression is upregulated in the early events of chondrocyte differentiation

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 245-251
Author(s):  
R. Quarto ◽  
B. Dozin ◽  
P. Bonaldo ◽  
R. Cancedda ◽  
A. Colombatti
Keyword(s):  
Suspension Culture ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Type I ◽  
Type Ii ◽  
Type Vi Collagen ◽  
Full Spectrum ◽  
Collagen Expression ◽  
Hypertrophic Chondrocyte

Dedifferentiated chondrocytes cultured adherent to the substratum proliferate and synthesize large amounts of type I collagen but when transferred to suspension culture they decrease proliferation, resume the chondrogenic phenotype and the synthesis of type II collagen, and continue their maturation to hypertrophic chondrocyte (Castagnola et al., 1986, J. Cell Biol. 102, 2310–2317). In this report, we describe the developmentally regulated expression of type VI collagen in vitro in differentiating avian chondrocytes. Type VI collagen mRNA is barely detectable in dedifferentiated chondrocytes as long as the attachment to the substratum is maintained, but increases very rapidly upon passage of the cells into suspension culture reaching a peak after 48 hours and declining after 5–6 days of suspension culture. The first evidence of a rise in the mRNA steady-state levels is obtained already at 6 hours for the alpha 3(VI) chain. Immunoprecipitation of metabolically labeled cells with type VI collagen antibodies reveals that the early mRNA rise is paralleled by an increased secretion of type VI collagen in cell media. Induction of type VI collagen is not the consequence of trypsin treatment of dedifferentiated cells since exposure to the actin-disrupting drug cytochalasin or detachment of the cells by mechanical procedures has similar effects. In 13-day-old chicken embryo tibiae, where the full spectrum of the chondrogenic differentiation process is represented, expression of type VI collagen is restricted to the articular cartilage where chondrocytes developmental stage is comparable to stage I (high levels of type II collagen expression).(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital Dyserythropoietic Anemia

PEDIATRICS ◽  
1973 ◽  
Vol 51 (5) ◽  
pp. 957-958
Author(s):  
G. Bennett Humphrey ◽  
Bahaod-Din Mojab ◽  
Ingomar Mutz
Keyword(s):  
Carbohydrate Metabolism ◽  
Morphological Characteristics ◽  
Type I ◽  
Type Ii ◽  
Congenital Dyserythropoietic Anemia ◽  
The 1950S ◽  
Deja Vu ◽  
Déjà Vu ◽  
Excellent Article

Reading the excellent article by Drs. Murphy and Oski, "Congenital Dyserythropoietic Anemia (CDA)",1 which further defines type II, produced a sense of deja vu. In the 1950s, nonspherocytic, hemolytic anemias (HNHA) were categorized as type I and II based on the in vitro autohemolysis test.2 This group of anemias has subsequently been demonstrated to be due to a series of enzymatic abnormalities in carbohydrate metabolism.3 In CDA, the morphological characteristics which define types I, II, and III probably reflect nuclear rather than cytoplasmic abnormalities.

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